Exploiting Interfacial Design for the Electrocatalytic Construction of C-C bonds

利用界面设计电催化构建 C-C 键

• 批准号: 10713693
• 负责人: Anna Wuttig
• 金额: $ 34.41万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10713693
• 关键词: Adopted; Adoption; Alcohols; Aldehydes; Chemicals; Complex; Coupling; Disease; Electricity; Electrodes; Elements; Generations; Ketones; Medicine; Methods; Pharmacologic Substance; Preparation; Property; Reaction; Research; Solid; design; drug development; drug discovery; forging; functional group; improved; interfacial; prevent; programs

PROJECT ABSTRACT The objective of our research is to access new chemical spaces in drug discovery and development by reimagining the catalytic conditions for electricity-driven organic transformations. We propose a synthetic platform to couple every major class of C(sp3) organic halide electrophile with aldehyde and ketones. By fine- tuning the key electrophile interactions with the electrode material by interfacial design, we propose to forge C(sp3)–C(sp3) bonds with high selectivity and stereoselectivity. Our approach will provide direct and catalytic access to new chiral alcohol and α,α-difluorobenzylic derivatives, prevalent motifs in several high-profile pharmaceuticals, from accessible feedstocks. Our synthetic methods will provide complementary and direct approaches to access (enantio)selective C(sp3)–C(sp3) bonds that are restricted to non-catalytic or multi-step reactions. Non-catalytic reactions require either the generation of highly reactive reaction intermediates that degrade bioactive functional groups or the use of expensive and rare elements that limit wide-spread adoption. In addition to increasing the accessibility to prepare and diversify pharmaceuticals via electrocatalytic C(sp3)– C(sp3) bond formation, our mechanistic and structural analyses of electrified interfaces will dissect the fundamental properties that control interfacial reactivity in complex electrosynthetic manifolds. Thus, our program will reveal how new mechanisms to construct C(sp3)–C(sp3) can be accessed by engaging a recoverable and infinitely reusable solid electrocatalyst interface; an inherently sustainable synthetic approach that can be readily adoptable by medicinal chemists.

项目摘要